The broad objectives are to determine the mechanisms by which the synthesis and metabolism of fatty acids, triglyceride and very low density lipoprotein (VLDL) are regulated in the adipocyte and liver cell with particular emphasis on the actions of insulin, glucagon, and cAMP. Two hormone-responsive cell culture systems will serve as in vivo models, a chick liver cell monolayer culture system developed in our laboratory and an established line of differentiating preadipocytes. The problem will be approached at three levels: 1. Hormone (insulin)-cell receptor interactions: The objectives are to determine the mechanism(s) by which insulin receptor level and activity are controlled in the differentiating preadipocyte and liver cell; to investigate the processes of insulin receptor synthesis, processing, insertion, and turnover by density-shift and photoaffinity labeling techniques. 2. Fatty acid synthesis and metabolism: The objectives are to determine the mechanism of long-term induction by insulin (and its curtailment by glucagon or cAMP) of acetyl-CoA carboxylase and fatty acid synthesis in liver cells from fasted animals; to determine the mechanism of acute control of fatty acid synthesis by glucagon or cAMP in the liver cell and preadipocyte; to determine the origin and mechanisms of assembly and glucagon-activated mobilization of cytoplasmic triglyceride-rich vesicles in the liver cell. 3. Regulation of the synthesis, processing, assembly, and secretion of very low density lipoprotein (VLDL): The objectives are to characterize the steps in synthesis, processing, and assembly of VLDL; to determine the nature of the recently-discovered lysyl derivative in apolipoprotein B and its possible role in the cross-linking of "precursor" apolipoprotein B; to determine how the VLDL pathway is regulated.